Abstract
With the current reproducibility of proteome preparation workflows along with the speed and sensitivity of the mass spectrometers, the transition of the mass spectrometry (MS)-based proteomics technology from biomarker discovery to clinical implementation is under appraisal in the biomedicine community. Therefore, this technology might be implemented soon to detect well-known biomarkers in cancers and other diseases. Acute myeloid leukemia (AML) is an aggressive heterogeneous malignancy that requires intensive treatment to cure the patient. Leukemia relapse is still a major challenge even for patients who have favorable genetic abnormalities. MS-based proteomics could be of great help to both describe the proteome changes of individual patients and identify biomarkers that might encourage specific treatments or clinical strategies. Herein, we will review the advances and availability of the MS-based proteomics strategies that could already be used in clinical proteomics. However, the heterogeneity of complex diseases as AML requires consensus to recognize AML biomarkers and to establish MS-based workflows that allow their unbiased identification and quantification. Although our literature review appears promising towards the utilization of MS-based proteomics in clinical AML in a near future, major efforts are required to validate AML biomarkers and agree on clinically approved workflows.
Highlights
In the last two decades, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technologies have provided a large number of candidate biomarkers in many diseases
As we have described in previous chapters, MS-based proteomics research is a very dynamic field characterized by continuous improvements of sample preparation protocols compatible with LC-MS/MS and the quick development of faster and more sensitive mass spectrometers
Apart from the identification and quantification of a disease’s proteome and relevant protein modifications as phosphorylation in global biomarker discovery studies with dependent acquisition (DDA) and data-independent acquisition (DIA) methodologies, validated and specific disease biomarkers can be quantified by MRM conducted on triple quadrupole instruments or parallel reaction monitoring (PRM) on Q-TOF and Orbitrap instruments, respectively [141]
Summary
In the last two decades, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technologies have provided a large number of candidate biomarkers in many diseases. That comprised of an initial untargeted exploration of the plasma proteome resulting in a list of potential biomarkers, followed by a quality assessment of candidate biomarkers and the combination of some of them into a classifier score with clinical utility Both internal validation -by multiple reaction monitoring mass-spectrometry (MRM-MS), enzyme-linked immune-sorbent assay (ELISA) and immunonephelometric assay (INA) as in this study- and validation of the classifier score on large external cohorts were required before clinical implementation. MS-based proteomics has been mainly employed in discovery approaches in the past years, it is becoming more and more used as a validation approach of biomarker candidates and applied to routine diagnostics and prognostics in the clinic by examining predetermined peptides according to the targeted proteomics strategy. Furtheramndorceh,edmuorsienngsittihvietylainstAdMecLahdaes,bteheenbeixotelonsgiivcealyl hsteutdeireodgaenndeimtyanwyipthosrseibgleartdhetroapleeuutkicesmtraotgeegnieessis and chemoshtehanovsueigtbhiveeiftnoyusriungdAgifefMsetreLednhtbaaasspebpdreoeoanncheeexxspteewnriesmrieveenrlteyaclesnitntulydviitaerpdopaarnonvddeidmn favonirvyoApsMtouLsdsiitebrselea[t2tm1h–ee2nr3ta],.ptHehueostweicesvstetrrra,atetegevigeenises have been suingcgluedsteeddmboareseodptoimnael uxspeeorfimweelnl-ktanloiwnnvdirturogsaonrddriungvs itvhaot scatundbeieusse[2d1o–n2ly3]f.orHsuobwseetvs oefr,peavtieenntsthough four diff[2e4r–e3n2t].approaches were recently approved for AML treatment, these strategies included more optimal use of well-known drugs or drugs that can be used only for subsets of patients [24,25,26,27,28,29,30,31,32]
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